Amino Acids, Glucose Metabolism and Clinical Relevance for Phenylketonuria Management

Review Article

Ann Nutr Disord & Ther. 2015; 2(3): 1026.

Amino Acids, Glucose Metabolism and Clinical Relevance for Phenylketonuria Management

Pena MJ1, Rocha JC1,2,3 and Borges N3,4*

1Medical Genetics Center Doctor Jacinto de Magalhães, Portugal

2Faculty of Health Sciences, University Fernando Pessoa, Portugal

3Center for Health Technology and Services Research, Portugal

4Faculty of Sciences Nutrition and Food, University of Porto, Portugal

*Corresponding author: Nuno Borges; Faculty of Science, Nutrition and Food Science, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal

Received: February 20, 2015; Accepted: August 12, 2015; Published: September 21, 2015

Abstract

It is general knowledge that glycaemia is affected by digested nutrients. Amino acids intake appears to be an important regulator in this regard. Many questions need to be answered, such as the real mediators of this response and the mechanisms underlying this metabolic behavior. Studies have been undertaken in order to investigate the role of amino acids on metabolic parameters. Their main findings suggest that the ingestion of free amino acids have a pivotal role in avoiding glycaemia excursions, improving glucose tolerance. In parallel, several important molecules for glucose metabolism have been exploited. Insulin and glucagon-like peptide – 1 (GLP-1) release seem to be the main triggers of this response. This insulinogenic effect is attributed to some amino acids, particularly the branched-chain amino acids (leucine, isoleucine and valine). GLP-1 may exert its effects by activating its receptor in pancreas and enhancing insulin release by β-cells or through its extrapancreatic actions. The mechanisms that may justify the aforementioned effects remain to be answered, being the mTOR pathway activation a possible key. These metabolic effects may have a special interest within the nutritional management of Phenylketonuria (PKU), an inborn metabolic disease of phenylalanine (Phe) catabolism. Since a Phe restricted diet is the mainstay of PKU treatment, a chronic supplementation with a Phe-free amino acid mixture is used. Although scientific evidence is scarce, it is hypothesized whether this chronic ingestion may modulate glycaemia.

Keywords: Amino acids; Glycaemia; Insulin; Glucagon-like peptide-1; Phenylketonuria

Abbreviations

GIP: Glucose-dependent Insulinotropic Polypeptide; GLP-1: Glucagon-Like Peptide-1; mTOR: Mammalian Target of Rapamycin; DPP-IV: Dipeptidyl Peptidase IV; PKU: Phenylketonuria; Phe: Phenylalanine; BH4: Tetrahydrobiopterin

Introduction

Glucose homeostasis, in a holistic perspective, is the set of responses that maintains the blood glucose levels within the physiological range. However, glucose homeostasis goes beyond the simple concept of glucose dynamics and implies the activation of different organic systems and the recruitment of several hormones [1]. Glucose as the prime fuel for some cells and tissues, such as brain, is a core molecule for human metabolism [2]. Along with this, it is foreseeable that impairment in glycaemia can result in diabetes, the paradigm of glucose metabolism disturbances. The long-term complications associated with these metabolic imbalances contribute to multi-organ injury, highlighting the importance of blood glucose management [2].

The effect of amino acids on glucose metabolism has been documented for years [3] but the mechanisms underlying this interaction are quite complex and not completely understood [4]. Amino acid intake may have a pivotal role on glucose homeostasis, exhibiting glucose-lowering effects [5,6] suggesting that amino acids intake with meals may mitigate glycemic fluctuations [7]. The explanation brought forward to elucidate this response is a higher insulin secretion, as studied either in humans [8] or animals [5]. Out of all essential amino acids, branched-chain amino acids (leucine, isoleucine and valine) [9], appear to act as potent insulin secretagogues, with special emphasis to leucine [10]. Furthermore, we should also keep in mind that nutrients, including amino acids, may modulate the synthesis of hormones at the gut level. These are capable of modulating glycaemia by boosting insulin release or through a direct effect, not closely associated with pancreatic metabolism [11]. These substances are called in cretins. The most recognized in cretins are Glucose-dependent Insulinotropic Polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) [12]. The crosstalk between amino acids, glucose, insulin and GLP-1 is illustrated on Figure 1.

Citation: Pena MJ, Rocha JC and Borges N. Amino Acids, Glucose Metabolism and Clinical Relevance for Phenylketonuria Management. Ann Nutr Disord & Ther. 2015; 2(3): 1026. ISSN : 2381-8891